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Reviewed, UniProtKB/Swiss-Prot P20020 (AT2B1_HUMAN)

Last modified November 3, 2009. Version 113. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Plasma membrane calcium-transporting ATPase 1
      Short name=PMCA1
    EC=3.6.3.8
Alternative name(s):
    Plasma membrane calcium pump isoform 1
    Plasma membrane calcium ATPase isoform 1
Gene names
Name: ATP2B1
Synonyms: PMCA1
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1258 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium out of the cell.

Catalytic activity

ATP + H2O + Ca2+(Cis) = ADP + phosphate + Ca2+(Trans).

Subcellular location

Cell membrane; Multi-pass membrane protein.

Tissue specificity

Isoform B is ubiquitously expressed. Isoform c is found in brain cortex, skeletal muscle and heart muscle. Isoform D has only been found in fetal skeletal muscle. Isoform k has been found in small intestine and liver.

Domain

The calmodulin-binding subdomain B is different in the different splice variants and shows pH dependent calmodulin binding properties in isoforms A, C, D and E.

Sequence similarities

Belongs to the cation transport ATPase (P-type) family. Type IIB subfamily.

Alternative products

This entry describes 6 isoforms produced by alternative splicing. [Align] [Select]
Isoform D (identifier: P20020-1)

Also known as: CIV;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform A (identifier: P20020-2)

Also known as: CII;

The sequence of this isoform differs from the canonical sequence as follows:
     1156-1258: IRVVNAFRSS...SPLHSLETSL → VVFSSSTASTTVGYSSGECIS
Isoform B (identifier: P20020-3)

Also known as: CI;

The sequence of this isoform differs from the canonical sequence as follows:
     1118-1155: Missing.
Isoform C (identifier: P20020-4)

Also known as: CIII;

The sequence of this isoform differs from the canonical sequence as follows:
     1147-1155: Missing.
Isoform E (identifier: P20020-5)

Also known as: CV;

The sequence of this isoform differs from the canonical sequence as follows:
     1156-1258: IRVVNAFRSS...SPLHSLETSL → VVFSSSTASTTVGFEW
Isoform K (identifier: P20020-6)

The sequence of this isoform differs from the canonical sequence as follows:
     1021-1056: Missing.
     1118-1155: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 12581258Plasma membrane calcium-transporting ATPase 1
PRO_0000046209

Regions

Topological domain1 – 9797Cytoplasmic Potential
Transmembrane98 – 11821 Potential
Topological domain119 – 15436Extracellular Potential
Transmembrane155 – 17521 Potential
Topological domain176 – 366191Cytoplasmic Potential
Transmembrane367 – 38620 Potential
Topological domain387 – 41933Extracellular Potential
Transmembrane420 – 43718 Potential
Topological domain438 – 852415Cytoplasmic Potential
Transmembrane853 – 87220 Potential
Topological domain873 – 88210Extracellular Potential
Transmembrane883 – 90321 Potential
Topological domain904 – 92320Cytoplasmic Potential
Transmembrane924 – 94623 Potential
Topological domain947 – 96418Extracellular Potential
Transmembrane965 – 98622 Potential
Topological domain987 – 100519Cytoplasmic Potential
Transmembrane1006 – 102722 Potential
Topological domain1028 – 103710Extracellular Potential
Transmembrane1038 – 105922 Potential
Topological domain1060 – 1258199Cytoplasmic Potential
Region1100 – 111718Calmodulin-binding subdomain A
Region1118 – 112710Calmodulin-binding subdomain B
Compositional bias296 – 2994Poly-Glu

Sites

Active site47514-aspartylphosphate intermediate
Metal binding7971Magnesium By similarity
Metal binding8011Magnesium By similarity

Amino acid modifications

Modified residue171Phosphoserine Ref.13
Modified residue11161Phosphothreonine; by PKC
Modified residue11931Phosphoserine Ref.13 Ref.12
Modified residue12031Phosphothreonine Ref.13
Modified residue12161Phosphoserine; by PKA Ref.13 Ref.12
Modified residue12201Phosphoserine Ref.13 Ref.12
Modified residue12461Phosphoserine Ref.13
Modified residue12491Phosphoserine Ref.13
Modified residue12531Phosphoserine Ref.13
Modified residue12561Phosphothreonine Ref.13
Modified residue12571Phosphoserine Ref.13

Natural variations

Alternative sequence1021 – 105636Missing in isoform K.
VSP_000372
Alternative sequence1118 – 115538Missing in isoform B and isoform K.
VSP_000373
Alternative sequence1147 – 11559Missing in isoform C.
VSP_000374
Alternative sequence1156 – 1258103IRVVN…LETSL → VVFSSSTASTTVGYSSGECI S in isoform A.
VSP_000375
Alternative sequence1156 – 1258103IRVVN…LETSL → VVFSSSTASTTVGFEW in isoform E.
VSP_000376
Natural variant2671M → R Rare polymorphism. Ref.14
VAR_000698

Experimental info

Sequence conflict259 – 2624LLLS → MSAT in AAA36000. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform D (CIV) [UniParc].

Last modified June 1, 2001. Version 3.
Checksum: 7037112747FC9B0A

FASTA1,258138,755
        10         20         30         40         50         60 
MGDMANNSVA YSGVKNSLKE ANHDGDFGIT LAELRALMEL RSTDALRKIQ ESYGDVYGIC 

        70         80         90        100        110        120 
TKLKTSPNEG LSGNPADLER REAVFGKNFI PPKKPKTFLQ LVWEALQDVT LIILEIAAIV 

       130        140        150        160        170        180 
SLGLSFYQPP EGDNALCGEV SVGEEEGEGE TGWIEGAAIL LSVVCVVLVT AFNDWSKEKQ 

       190        200        210        220        230        240 
FRGLQSRIEQ EQKFTVIRGG QVIQIPVADI TVGDIAQVKY GDLLPADGIL IQGNDLKIDE 

       250        260        270        280        290        300 
SSLTGESDHV KKSLDKDPLL LSGTHVMEGS GRMVVTAVGV NSQTGIIFTL LGAGGEEEEK 

       310        320        330        340        350        360 
KDEKKKEKKN KKQDGAIENR NKAKAQDGAA MEMQPLKSEE GGDGDEKDKK KANLPKKEKS 

       370        380        390        400        410        420 
VLQGKLTKLA VQIGKAGLLM SAITVIILVL YFVIDTFWVQ KRPWLAECTP IYIQYFVKFF 

       430        440        450        460        470        480 
IIGVTVLVVA VPEGLPLAVT ISLAYSVKKM MKDNNLVRHL DACETMGNAT AICSDKTGTL 

       490        500        510        520        530        540 
TMNRMTVVQA YINEKHYKKV PEPEAIPPNI LSYLVTGISV NCAYTSKILP PEKEGGLPRH 

       550        560        570        580        590        600 
VGNKTECALL GLLLDLKRDY QDVRNEIPEE ALYKVYTFNS VRKSMSTVLK NSDGSYRIFS 

       610        620        630        640        650        660 
KGASEIILKK CFKILSANGE AKVFRPRDRD DIVKTVIEPM ASEGLRTICL AFRDFPAGEP 

       670        680        690        700        710        720 
EPEWDNENDI VTGLTCIAVV GIEDPVRPEV PDAIKKCQRA GITVRMVTGD NINTARAIAT 

       730        740        750        760        770        780 
KCGILHPGED FLCLEGKDFN RRIRNEKGEI EQERIDKIWP KLRVLARSSP TDKHTLVKGI 

       790        800        810        820        830        840 
IDSTVSDQRQ VVAVTGDGTN DGPALKKADV GFAMGIAGTD VAKEASDIIL TDDNFTSIVK 

       850        860        870        880        890        900 
AVMWGRNVYD SISKFLQFQL TVNVVAVIVA FTGACITQDS PLKAVQMLWV NLIMDTLASL 

       910        920        930        940        950        960 
ALATEPPTES LLLRKPYGRN KPLISRTMMK NILGHAFYQL VVVFTLLFAG EKFFDIDSGR 

       970        980        990       1000       1010       1020 
NAPLHAPPSE HYTIVFNTFV LMQLFNEINA RKIHGERNVF EGIFNNAIFC TIVLGTFVVQ 

      1030       1040       1050       1060       1070       1080 
IIIVQFGGKP FSCSELSIEQ WLWSIFLGMG TLLWGQLIST IPTSRLKFLK EAGHGTQKEE 

      1090       1100       1110       1120       1130       1140 
IPEEELAEDV EEIDHAEREL RRGQILWFRG LNRIQTQMDV VNAFQSGSSI QGALRRQPSI 

      1150       1160       1170       1180       1190       1200 
ASQHHDVTNI STPTHIRVVN AFRSSLYEGL EKPESRSSIH NFMTHPEFRI EDSEPHIPLI 

      1210       1220       1230       1240       1250 
DDTDAEDDAP TKRNSSPPPS PNKNNNAVDS GIHLTIEMNK SATSSSPGSP LHSLETSL 

« Hide

Isoform A (CII).

Checksum: 5672202C16491703
Show »

FASTA1,176129,516
Isoform B (CI).

Checksum: 7E75C19B1A501423
Show »

FASTA1,220134,685
Isoform C (CIII).

Checksum: 8F56F132BE096587
Show »

FASTA1,249137,804
Isoform E (CV).

Checksum: 9FC9B1AA3B32B384
Show »

FASTA1,171129,152
Isoform K.

Checksum: B1FB3E7116D2FDA2
Show »

FASTA1,184130,617

References

« Hide 'large scale' references
[1]"Complete primary structure of a human plasma membrane Ca2+ pump."
Verma A.K., Filoteo A.G., Stanford D.R., Wieben E.D., Penniston J.T., Strehler E.E., Fischer R., Heim R., Vogel G., Mathews S., Strehler-Page M.-A., James P., Vorherr T.E., Krebs J., Carafoli E.
J. Biol. Chem. 263:14152-14159(1988) [PubMed: 2844759] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B).
Tissue: Erythrocyte.
[2]"Molecular cloning of a plasma membrane calcium pump from human osteoblasts."
Kumar R., Haugen J.D., Penniston J.T.
J. Bone Miner. Res. 8:505-513(1993) [PubMed: 8386431] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B).
Tissue: Osteoblast.
[3]"Structure of the gene encoding the human plasma membrane calcium pump isoform 1."
Hilfiker H., Strehler-Page M.-A., Stauffer T.P., Carafoli E., Strehler E.E.
J. Biol. Chem. 268:19717-19725(1993) [PubMed: 8396145] [Abstract]
Cited for: PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS A AND B).
Tissue: Leukocyte.
[4]Strehler E.E., Strehler-Page M.-A.
Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION.
[5]"mRNAs for plasma membrane calcium pump isoforms differing in their regulatory domain are generated by alternative splicing that involves two internal donor sites in a single exon."
Strehler E.E., Strehler-Page M.-A., Vogel G., Carafoli E.
Proc. Natl. Acad. Sci. U.S.A. 86:6908-6912(1989) [PubMed: 2528729] [Abstract]
Cited for: PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS A; C AND D).
Tissue: Fetal skeletal muscle.
[6]"Study of calmodulin binding to the alternatively spliced C-terminal domain of the plasma membrane Ca2+ pump."
Kessler F., Falchetto R., Heim R., Meili R., Vorherr T.E., Strehler E.E., Carafoli E.
Biochemistry 31:11785-11792(1992) [PubMed: 1332771] [Abstract]
Cited for: PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
Tissue: Fetal brain.
[7]"Quantitative analysis of alternative splicing options of human plasma membrane calcium pump genes."
Stauffer T.P., Hilfiker H., Carafoli E., Strehler E.E.
J. Biol. Chem. 268:25993-26003(1993) [PubMed: 8245032] [Abstract]
Cited for: PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND E).
Tissue: Brain cortex.
[8]Erratum
Stauffer T.P., Hilfiker H., Carafoli E., Strehler E.E.
J. Biol. Chem. 269:32022-32022(1994) [PubMed: 7989379] [Abstract]
[9]"Human and rat intestinal plasma membrane calcium pump isoforms."
Howard A., Legon S., Walters J.R.
Am. J. Physiol. 265:G917-G925(1993) [PubMed: 7694502] [Abstract]
Cited for: ALTERNATIVE SPLICING (ISOFORM K).
Tissue: Small intestine mucosa.
[10]"Primary structure of the cAMP-dependent phosphorylation site of the plasma membrane calcium pump."
James P.H., Pruschy M., Vorherr T.E., Penniston J.T., Carafoli E.
Biochemistry 28:4253-4258(1989) [PubMed: 2548572] [Abstract]
Cited for: PHOSPHORYLATION BY CAMP KINASE.
[11]"Protein kinase C phosphorylates the carboxyl terminus of the plasma membrane Ca(2+)-ATPase from human erythrocytes."
Wang K.K.W., Wright L.C., Machan C.L., Allen B.G., Conigrave A.D., Roufogalis B.D.
J. Biol. Chem. 266:9078-9085(1991) [PubMed: 1827443] [Abstract]
Cited for: PHOSPHORYLATION BY PROTEIN KINASE C.
[12]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed: 17081983] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1193; SER-1216 AND SER-1220, MASS SPECTROMETRY.
Tissue: Epithelium.
[13]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-17; SER-1193; THR-1203; SER-1216; SER-1220; SER-1246; SER-1249; SER-1253; THR-1256 AND SER-1257, MASS SPECTROMETRY.
[14]"Investigation of the Met-267 Arg exchange in isoform 1 of the human plasma membrane calcium pump in patients with essential hypertension by the amplification-created restriction site technique."
Benkwitz C., Kubsisch C., Kraft K., Neyses L.
J. Mol. Med. 75:62-66(1997) [PubMed: 9020386] [Abstract]
Cited for: VARIANT ARG-267.
+Additional computationally mapped references.

Cross-references

Sequence databases

J04027 mRNA. Translation: AAA74511.1.
M95541 mRNA. Translation: AAA35999.1.
M95542 mRNA. Translation: AAA36000.1.
L14561 Genomic DNA. Translation: AAD09924.1.
L14561 Genomic DNA. Translation: AAD09925.1.
M25824 Genomic DNA. Translation: AAA58383.1.
M25824 Genomic DNA. Translation: AAA58382.1.
M25824 Genomic DNA. Translation: AAA58381.1.
S49852 mRNA. Translation: AAB24324.1.
U15686 mRNA. Translation: AAA60983.1.
U15687 mRNA. Translation: AAA60984.1.
IPIIPI00021695.
IPI00216526.
IPI00216527.
IPI00216528.
IPI00216529.
IPI00216530.
PIRA30802.
E49570.
I55491.
I70165.
RefSeqNP_001001323.1.
NP_001673.2.
UniGeneHs.506276

3D structure databases

ModBaseSearch...

Protein-protein interaction databases

STRINGP20020.

PTM databases

PhosphoSiteP20020.

Proteomic databases

PRIDEP20020.

Genome annotation databases

EnsemblENST00000261173; ENSP00000261173; ENSG00000070961; Homo sapiens. [Genome view]
ENST00000348959; ENSP00000343599; ENSG00000070961; Homo sapiens. [Genome view]
ENST00000359142; ENSP00000352054; ENSG00000070961; Homo sapiens. [Genome view]
ENST00000393164; ENSP00000376869; ENSG00000070961; Homo sapiens. [Genome view]
ENST00000428670; ENSP00000392043; ENSG00000070961; Homo sapiens. [Genome view]
GeneID490.
KEGGhsa:490.
UCSCuc001tbg.1. human.
uc001tbh.1. human.

Organism-specific databases

CTD490.
GeneCardsGC12M088484.
H-InvDBHIX0010871.
HGNCHGNC:814. ATP2B1.
HPACAB005605.
HPA011166.
HPA012945.
MIM108731. gene.
PharmGKBPA25107.
GenAtlasSearch...

Phylogenomic databases

HOVERGENP20020.
OMAIPEEALY.

Enzyme and pathway databases

BRENDA3.6.3.8. 247.

Gene expression databases

ArrayExpressP20020.
BgeeP20020.
CleanExHS_ATP2B1.
GenevestigatorP20020.
GermOnlineENSG00000070961. Homo sapiens.

Family and domain databases

InterProIPR008250. ATPase_P-typ_ATPase-assoc-reg.
IPR006408. ATPase_P-typ_Ca-transp_PMCA.
IPR006068. ATPase_P-typ_cation-transptr_C.
IPR004014. ATPase_P-typ_cation-transptr_N.
IPR001757. ATPase_P-typ_ion-transptr.
IPR018303. ATPase_P-typ_P_site.
IPR005834. Dehalogen-like_hydro.
[Graphical view]
PANTHERPTHR11939. ATPase_P. 1 hit.
PfamPF00689. Cation_ATPase_C. 1 hit.
PF00690. Cation_ATPase_N. 1 hit.
PF00122. E1-E2_ATPase. 1 hit.
PF00702. Hydrolase. 1 hit.
[Graphical view]
PRINTSPR00119. CATATPASE.
TIGRFAMsTIGR01517. ATPase-IIB_Ca. 1 hit.
TIGR01494. ATPase_P-type. 4 hits.
PROSITEPS00154. ATPASE_E1_E2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio2053.
SOURCESearch...

Entry information

Entry nameAT2B1_HUMAN
AccessionPrimary (citable) accession number: P20020
Secondary accession number(s): Q12992 expand/collapse secondary AC list , Q12993, Q13819, Q13820, Q13821, Q16504, Q93082
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: June 1, 2001
Last modified: November 3, 2009
This is version 113 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

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List of human entries with polymorphisms or disease mutations

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Index of human polymorphisms and disease mutations

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Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents